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Participating Organization(s) |
National Institutes of Health (NIH) |
National Cancer Institute (NCI) |
Funding Opportunity Title |
NCI Experimental Therapeutics-Clinical Trials Network with Phase 1 Emphasis (ET-CTN) (UM1) |
Activity Code |
UM1 Multi-Component Research Project Cooperative Agreements |
Announcement Type |
Reissue of RFA-CA-07-031 |
Related Notices |
Funding Opportunity Announcement (FOA) Number |
Companion Funding Opportunity |
Not Applicable |
Only one application per institution may be submitted in response to this FOA; see Section III. 3. Additional Information on Eligibility. |
Catalog of Federal Domestic Assistance (CFDA) Number(s) |
93.395 |
Funding Opportunity Purpose |
The purpose of this Funding Opportunity Announcement (FOA) issued by the National Cancer Institute (NCI) is to support an experimental therapeutics clinical trials program through the creation of a consolidated, integrated NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN). This FOA solicits UM1 cooperative agreement applications for multidisciplinary groups that will conduct early phase experimental therapeutics clinical trials. Members of the ET-CTN will work on investigational agent-specific trans-network project teams to define the drug development plan, and to conduct experimental therapeutic clinical trials filed to the Investigational New Drug (IND) applications by NCI's Division of Cancer Treatment and Diagnosis (DCTD), Cancer Therapy Evaluation Program (CTEP). The ultimate purpose of the ET-CTN is to define better approaches to the development of novel anticancer agents that capitalize on the ability to characterize tumors molecularly and find appropriate biomarkers to select patients most likely to respond to specific agents. The clinical trials to be conducted by the ET-CTN are intended to provide the dose, schedule, and early evidence of activity that will help guide disease-specific clinical trials to be conducted by the National Clinical Trials Network (NCTN), which will focus on controlled, randomized, Phase 3 trials. |
Posted Date |
February 8, 2013 |
Letter of Intent Due Date(s) |
March 23, 2013 |
Application Due Date(s) |
August 23, 2013 |
AIDS Application Due Date(s) |
Not Applicable |
Scientific Merit Review |
October - November 2013 |
Advisory Council Review |
January 2014 |
Earliest Start Date |
February 2014 |
Expiration Date |
August 24, 2013 |
Due Dates for E.O. 12372 |
Not Applicable |
Required Application Instructions
It is critical that applicants follow the instructions in the PHS 398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH's multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH's Applying Electronically website.
Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
The purpose of this Funding Opportunity Announcement (FOA) is to transform the NCI-sponsored cooperative experimental therapeutics clinical trials program from a series of separate organizations conducting early phase cancer treatment trials into a consolidated, integrated NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN). Members of the ET-CTN will work on investigational agent-specific trans-network project teams to define the drug development plan, and conduct experimental therapeutic clinical trials for agents with Investigational New Drug applications (INDs) held by the NCI Division of Cancer Treatment and Diagnosis (DCTD), Cancer Therapy Evaluation Program (CTEP, http://ctep.cancer.gov/).
The clinical trials to be conducted by the ET-CTN are intended to provide the dose, schedule, and early evidence of therapeutic activity including "proof of concept", "proof of mechanism", and target engagement/inhibition that will help guide disease-specific trials to be conducted under other NCI-supported programs, including the National Clinical Trials Network (NCTN) which will focus on controlled, randomized, Phase 3 clinical trials.
The NCI will facilitate formation of multi-institutional, multi-disciplinary project teams to establish a development plan for a series of trials for each novel agent to answer important questions. A drug development plan for each agent will be evaluated by the Investigational Drug Steering Committee (IDSC) run by the Coordination Center for Clinical Trials (CCCT) out of the Office of the Director. The IDSC is composed of ET-CTN contact PDs/PIs (awardees), subject matter experts, NCTN representatives, statisticians, pharmacologists, and NCI staff members with expertise in optimal early drug development. NCI representatives serve as non-voting liaisons. Emphasis will be placed on understanding and assessing both the molecular target(s) of the agent being studied as well as developing appropriate biomarker assays to select patients whose tumors are most likely to respond to the agent. The ET-CTN will focus on the pharmacokinetics (PK)/pharmacodynamics (PD), biomarker assays, and molecular characterizations of the majority of patients enrolled on its clinical trials, with an initial emphasis on genomic evaluation. Drug development will include assays for PD to define target engagement by the investigational agent. Investigators will collaborate with each other and with NCI staff to achieve ET-CTN objectives. The projects outlined in the drug development plan will be submitted as protocols for final approval to CTEP's Protocol Review Committee (PRC). The ET-CTN will efficiently perform trials with new anticancer agents in compliance with the timelines established by the Operational Efficiency Working Group (OEWG).
ET-CTN members, sites, and selected external participants will have the opportunity to enroll patients on all trials conducted by the ET-CTN, irrespective of the specific ET-CTN site leading the trial. All participating sites will be responsible for monitoring and reporting patient safety information throughout the conduct of their clinical trials. NCI will provide standardized central operational, regulatory, and administrative support including data management, trial registration, and Central Institutional Review Board (CIRB) review for approved, early phase trials.
The goals of the ET-CTN include:
NCI's early therapeutics development program funds and oversees clinical development of new agents. The program has:
This program has been designed and implemented to ensure that: (1) early phase clinical trial designs can accommodate new therapeutic approaches; (2) early phase clinical trials are conducted safely and efficiently; and (3) potential doses and schedules are determined for use in patients in clinical trials to evaluate agent combinations and/or for Phase 2 testing. NCI currently sponsors 85 early phase clinical trials with novel agent combinations. Approximately two-thirds of the Phase 1 combination studies listed in ClinicalTrials.gov and in published literature have been conducted in the NCI Phase 1 program, which performs only cancer-relevant studies.
Through this program, the NCI promotes exploration of scientifically important clinically-relevant questions in areas that: (1) are not the primary focus of pharmaceutical companies; (2) involve investigational agent combination studies; (3) are aimed at maximizing target inhibition; (4) are aimed at abrogating signaling through parallel and complementary pathways in cancer cells; and (5) molecularly characterize patients tumors to further elucidate mechanisms of therapeutic response and/or resistance.
Through NCI's Experimental Therapeutics Program, 540 INDs for investigational agents have been filed since 1972. CTEP currently holds approximately 100 INDs for investigational oncology agents which involve 60 pharmaceutical/biotechnology collaborators. CTEP prepares and submits approximately eight to fifteen IND applications to the Food and Drug Administration (FDA) each year. Agents under evaluation include small molecules, antibodies, vaccines, targeted toxins, oligonucleotides, and gene transfer agents.
In recent years, there have been unprecedented increases in the accumulation of data on mutations, epigenetic changes, and other "-omics" aspects with potential significance for various oncogenic molecular pathways. This new information has led to the realization that assessing various cancer-relevant molecular abnormalities is essential for optimal and efficient development of targeted agents designed to exploit specific abnormalities in the therapeutic context. Combination studies with molecularly targeted agents have become an increasingly high priority for NCI, based upon evidence that resistance to initially effective single agents often develops quite rapidly in many adult tumors.
Overview of the Coordination of the Experimental Therapeutics Clinical Trials Network. To address the new opportunities and challenges in the development of novel targeted cancer therapeutics, the NCI has established a systematic approach with several interacting functional components. The NCI Experimental Therapeutics Program (NExT) is the portal through which NCI brings investigational agents into DCTD/CTEP for development. After a new agent is chosen for development, the Investigational Drug Branch (IDB) Project Team Leader will form an NCI Project Team from the various clinical, translational, and basic biology programs at NCI. Members of the Project Team will draft a preliminary drug/biomarker/assay development plan. Once this plan is reviewed and approved by the NCI Senior Advisory Committee (SAC), part of the NeXT-approved process, NCI will send out a request for Project Team Applications (PTAs) to the ET-CTN members, awardees of the NCI Phase 2 Contracts Program, NCTN awardees, and other appropriate investigators. The request for PTA will include publically available information about the drug being developed and the types and focus of the clinical trials being considered in the preliminary drug/biomarker/assay development plan. Once the PTAs have been reviewed and prioritized by NCI, the IDB Project Team Leader will constitute the Drug X Project Team with the PDs/PIs Lead Protocol Organization (LPOs), defined below, of the PTAs that have been approved as well as other relevant subject matter experts. This Drug X Project Team will be charged with refining the drug/biomarker/assay development plan for a team presentation to the IDSC. Following IDSC evaluation, the drug/biomarker/assay development plan will be finalized by the IDB and Letters of Intent (LOIs) will be requested from the Drug X project team. After approval of the LOIs by CTEP/DCTD, the protocols will be developed and submitted to DCTD/CTEP for final approval before activation.
NCI Organizational Groups Involved in the Early Experimental Therapeutics Clinical Trials Network
Several NCI organizational groups (branches/programs/services) will have important supporting roles in carrying out the research goals of the ET-CTN. The ET-CTN will be expected to interact as appropriate with such NCI branches/programs/services as: CTEP, Biometric Research Branch (BRB), Cancer Diagnosis Program (CDP), Cancer Trials Support Unit (CTSU), Central Institutional Review Board (CIB), Clinical Data Management System (CDMS), Clinical Trials Branch in the Cancer Imaging Program( CIP), Clinical Trials Monitoring Service (CTMS), Oncology Patient Enrollment Network, and Regulatory Support Service
For the context of this FOA, several terms are used in specific meaning as defined below.
Terms related to the organization of ET-CTN:
Other terms related to the ET-CTN
This FOA will support up to 10 ET-CTN sites dedicated to new agent developmental efforts with emphasis on early phase clinical trials. ET-CTN awards will provide the major resource for rapid, efficient, systematic evaluation and determination of optimal dose/schedule for specific agents and combinations of investigational agents sponsored under CTEP INDs. ET-CTN sites will also be expected to extensively characterize patient's tumors on a molecular level to select appropriate patients for specific treatments, and to explore mechanisms of resistance and response to assist in defining follow-on treatment or determine future combination therapies.
Scope of Scientific Activities. Consistent with the objectives and priorities of the ET-CTN, each proposed ET-CTN site and its investigators need to be capable of clinical research involving the following main scientific activities:
Multi-disciplinary, Agent-specific Project Teams. The ET-CTN is designed to accomplish its objectives by forming multi-institutional, multi-disciplinary Project Teams, which will define early drug development clinical trials of novel drugs and/or combination therapies. All ET-CTN awardees will be expected to participate on Project Teams to define the development plans for specific novel agents/combinations relevant to their expertise and capabilities. Representatives of other NCI-supported programs will also participate on those teams. The NCI will coordinate and support logistically the formation and operation of the Project Teams. As novel agents progress from Phase 1 to Phase 2 clinical trials, investigators representing various relevant NCI-supported programs will collaborate with NCI's Investigational Drug Steering Committee (IDSC) and its disease-specific steering committees. These Project Teams will develop novel treatments requiring molecularly guided patient selection and pathway-driven investigational combination therapies a wide variety of malignancies.
Additional NCI Support for the ET-CTN sites. The NCI/DCTD/CTEP will provide the ET-CTN awardees with standardized central operational, regulatory, and administrative support. This support will cover such activities as: data management, clinical trial registration, and Central Institutional Review Board (CIRB) review for approved, early phase trials.
Applicants responding to this FOA may include single or multiple institutions, as needed, to propose, develop, and perform early clinical trials, and to analyze the results of such trials. Each of the proposed functions of specific required organizational components for each ET-CTN site are outlined below.
Key Capabilities and Attributes of Required Components
For the outlined goals of ET-CTN, applicants responding to this FOA need to have appropriate capabilities and attributes. These aspects are defined below as key components that are expected to provide a scientific and organizational framework for the ET-CTN.
Experience in Conduct of Clinical Trials and Development of Experimental Therapeutic Agent
It is essential that investigators applying for the ET-CTN awards have considerable expertise and well documented experience and accomplishments (past performance) in the conduct of cancer clinical trials and clinical development of experimental therapeutics. This experience may be acquired through a past performance in the NCI Early Phase Clinical Trials Program with Phase 1 Emphasis. However, previous affiliation with the NCI Early Phase Clinical Trials Program with Phase I Emphasis is NOT required and all qualified applicants are encouraged to apply.
Scientific Leadership
Program Director(s)/Principal Investigator(s) (PDs/PIs) at the ET-CTN sites are expected to be national and international leaders in cancer related clinical trials of novel therapeutic agents, related clinical areas, and translational research relevant to such studies. PDs/PIs should also have documented administrative leadership experience. The emphasis is on a team science approach and the ability to establish productive collaborations among participating clinical and translational research investigators from the proposed ET-CTN site. ET-CTN awardees will be expected to interact with other ET-CTN sites as well as other relevant external programs. Each ET-CTN site will be required to establish a specific structure to oversee the conduct of early phase therapeutic clinical trials, ensure data safety monitoring, compliance with the required policies and regulations, and facilitate interactions with other ET-CTN and NCI staff.
Team Science for Project Development
Each ET-CTN site will be expected to lead and/or participate in multi-disciplinary scientific Project Teams formed during the development and implementation of ET-CTN drug development plans. This objective requires that ET-CTN investigators are highly capable of inter- and trans-disciplinary team-based research efforts, including potential for interactions with investigators from other ET-CTN sites, other NCI-sponsored programs, and NCI staff members.
Pharmacokinetic/Pharmacodynamic (PK/PD), Biomarker Assay, and Molecular Characterization of Patients
Each ET-CTN site must have the capability to support clinical trials by conducting various laboratory testing of clinical specimens as needed. In addition to the standard PK/PD determinations, the required capabilities include such aspects as: developing validated assays; using validated molecular imaging methods; ability to handle biospecimens for transfer to other ET-CTN sites or tumor banks/biorepositories; and participating in the molecular characterization of all patients enrolled on early phase therapeutics trials. The latter aspect includes the requisite expertise in acquiring fresh biopsy specimens from a high percentage of patients on trials (even if invasive procedures are required).
Coordination of Clinical Trials and Associated Activities
The research and managerial coordination component will be responsible for the organization and coordination for all aspects of clinical trials operations, implementation, and safe conduct. The administrative component shall collaborate with NCI support infrastructure to coordinate ET-CTN activities. (Key units of this supporting infrastructure are listed above in the Background section).
Research Pharmacy Management
It is essential that all ET-CTN sites have a dedicated component to conduct investigational drug pharmacy operations required to adequately fulfill obligations related to investigational agents.
Career Development and Mentored Training of Junior Investigators
Each ET-CTN site will be expected to organize appropriate career development and mentored training. The program should provide an adequate mentorship and/or training for new and junior investigators, including opportunities for trainees to lead clinical trials and participate in future ET-CTN activities and/or initiatives.
Funding Instrument |
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, and/or participate in project activities. |
Application Types Allowed |
New The OER Glossary and the PHS 398 Application Guide provide details on these application types. |
Funds Available and Anticipated Number of Awards |
NCI intends to fund approximately 10 awards, corresponding to a total cost of $8,500,000, for fiscal year 2014. Future year amounts will depend on annual appropriations. |
Award Budget |
Application budgets must not exceed $850,000 total costs/year. |
Award Project Period |
5 years |
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply but only if they are based in Canada.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply except for Canadian components.
Foreign components, as defined in
the NIH Grants Policy Statement, are allowed.
Only U.S. and Canadian institutions are eligible to apply. Other Foreign institutions may participate in the program through collaborations with either U.S. or Canadian applicant organizations.
Applicant organizations must complete the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least6 weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS 398 Application Guide.
Provided that other all other qualification requirements are met, the PD/PI or LAO PD(s)/PI(s) may have any of the following degrees: M.D., M.D./Ph.D., D.O., or Ph.D.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Only one application per institution may be submitted in response to this FOA.
NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
1. To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
2. Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
3. Of an application with a changed grant activity code.
Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.
It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
S. Percy Ivy, M.D.
Investigational Drug Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
NCI Shady Grove
Room 5W458, MSC 9725
9609 Medical Center Drive
Bethesda, MD 20892-9725 (for Express mail, use Rockville, MD 20850)
Telephone: (240) 276-6107
Email: firstname.lastname@example.com
Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
At the time of submission two additional copies of the application and all the Appendix
files must be sent to:
Referral Officer
Division of Extramural Activities
National Cancer Institute
9609 Medical Center Drive, Room 7W412
Bethesda, Maryland 20892-9750 (for Express mail, use Rockville, MD 20850)
Telephone: 240-276-6390
Fax: 240-276-7682
E-mail: email@example.com
All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed with the following exceptions or additional requirements.
Research Strategy must consists of the following sub-sections with the indicated page limits:
A. Overview of Relevant Capabilities and Past Performance 6 pages
B. Scientific Leadership & Site Organization 12 pages
C. Team Science for Project Development 6 pages
D. PK/PD, Biomarker Assays and Molecular Characterization of Patients 6 pages
E. Coordination of Clinical Trials and Associated Activities 12 pages
F. Research Pharmacy Management 6 pages
G. Career Development and Mentored Training of Junior Investigators - 6 pages
The following sections supplement the instructions found in the PHS 398 Application Guide.
The application should be assembled and paginated as one complete document in the following order:
Face Page
Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells
Detailed Budget for Initial Budget Period
Budget for Entire Proposed Period of Support
Budgets Pertaining to Consortium/Contractual Arrangements
Biographical Sketches
Research Plan
Specific Aims
Research Strategy with the following sub-sections:
Bibliography and References Cited
Protection of Human Subjects
Inclusion of Women and Minorities
Targeted/Planned Enrollment Table
Inclusion of Children
Vertebrate Animals
Select Agent Research
Multiple PD/PI Leadership Plan
Consortium/Contractual Arrangements
Letters of Support (e.g., Consultants)
Resource Sharing Plan
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions for the application parts listed below.
Modify Form Page 3 of the PHS 398 to replace standard sub-sections of "Research Strategy" with the following new sub-sections:
A. Overview of Relevant Capabilities and Past Performance
B. Scientific Leadership & Site Organization
C. Team Science for Project Development
D. PK/PD, Biomarker Assays and Molecular Characterization of Patients
E. Coordination of Clinical Trials and Associated Activities
F. Research Pharmacy Management
G. Career Development and Mentored Training of Junior Investigators
Follow the current PHS 398 instructions to provide a detailed budget (direct costs) for the entire application for the first 12-month period (Form page 4) and the entire proposed project period (Form page 5).
Use Additional Form Pages 4 and 5 to provide detailed separate budget information (first year and cumulative budgets for the entire project period) for the following individual application components:
Important Note on Budget: The requested budgets should take into consideration the standardized central operational, regulatory and administrative support provided by NCI. These services will be directly funded by the NCI and respective cost must not be included in the requested budgets.
The budget should include (in addition to support for scientific leadership, administrative and regulatory activities, data management and analysis, and travel, etc.) the following items:
1. Scientific Leadership and Site Organization Funds for travel. The LAO PD(s)/PI(s) will be required to travel to four IDSC meetings per year. Travel funds for two NCI/CTEP Early Drug Development (EDD) meetings per year for three representatives from the ET-CTN site (at least one of whom must be the LAO PD/PI and for two presenters for major national/international meetings should be included in the budget for Scientific Leadership.
2. PK/PD, Biomarker Assays, and Molecular Characterization Research Funds for laboratory studies (e.g., PK and PD studies) performed on specimens (e.g., blood, tumor tissue, buccal cells, etc.) obtained from participants enrolled on ET-CTN clinical trials. Include this within the PK/PD, Biomarker Assays, and Molecular Characterization of Patients budget pages. Note: Biomarker assays will be prioritized and funded separately through administrative supplements. Other biomarker assays will require other sources of funding.
Pharmacology and specimen acquisition to be allocated to support institutional costs of research that are not considered a cost of treatment by medical insurers, and therefore are not reimbursed by insurers (e.g., blood and urine collection and shipping for PK studies, tumor tissue handling and shipping to the tissue bank or pathology component, and performance of research imaging studies).
3. Coordination of Clinical Trials and Associated Activities Research Funds to be allocated to support institutional costs of research that are not considered a cost of treatment by medical insurers, and therefore are not reimbursed by insurers (e.g., blood and urine collection and shipping for PK studies, tumor tissue handling and shipping to the tissue bank, and performance of research imaging studies). Include this cost within the Coordination of Clinical Trials and Associate Activities budget pages.
The budget for early clinical trials of new anticancer agents with early-phase emphasis should include funding to be allocated to support research and development and ET-CTN collaboration (in addition to support for scientific leadership, administrative and regulatory activities, data management and analysis, etc.).
All costs for on-site data management using Medidata Rave and services provided by CTMS must be fully justified. The cost of mailing or handling research-related patient specimens, forms, and materials should be included. Other consulting costs should be outlined.
Coordination of Clinical Trials and Associated Activities (protocol development, and statistics and data management) for the institution(s) costs to support the non-accrual responsibilities associated with participating in early-phase experimental therapeutic clinical trials (e.g., CIRB submission, amendment distribution and continuing review, site training, pharmacy set-up, and site administration) that must be met even if patients are never enrolled on a study at an institution. An annual accrual rate of at least 50 patients per year should be assumed.
4. Career Development and Mentored Training of Junior Investigators Funds (approximately 3% of the total budget request) for activities to develop junior investigators/junior faculty through mentorship and other initiatives. Junior investigator career development and mentored training costs should be addressed in the research plan in the proposed budget.
Budgets for affiliated consortium component organizations (i.e., AOs ) must be provided as individual subcontractual budget pages following the PHS 398 instructions.
In addition to standard information, provide in this section documentation of important capabilities and available resources for specific functional components of the ET-CTN LAO. Relevant information may be provided in tabular form as listed below. Applicants are strongly encouraged to use, as appropriate, table templates provided at http://ctep.cancer.gov/investigatorResources/docs/RFA-CA-13-006_TABLE_TEMPLATES.PDF.
Template Table 1. Leadership Staffing: List the staff in specific leadership positions.
Template Table 2. Completed and Ongoing Phase 1 and Phase 2 Clinical Trials: List Phase 1clinical trials that have been completed during the last 5 years and of any ongoing clinical trials for which significant research findings are available. Include first-in-human studies and trials that determined dose and schedule for both single agents and investigational agent combinations. Phase 2 trial examples may be provided. A table is recommended that enumerates total actual accrual by year for each clinical trial described.
Template Table 3. Other Scientific Achievements for Clinical Trials
Template Table 4. List of PK/PD Assays and Molecular Characterizations Performed During Conduct of Early Phase Clinical Trials
Template Table 5. Summary Accrual for Screened and Treated Patients on All Early Experimental Therapeutic Clinical Trials.
Template Table 6. Summary of Letters of Intent (LOI) Submitted and Approved, and Protocols Submitted: List Phase 1 clinical trial protocol development activities during the last 5 years, including relevant dates and milestones for LOIs submitted, clinical trial protocols submitted, and clinical trials activated.
Template Table 7. Inclusion Enrollment Report: Provide data on annual patient accrual to early phase clinical trials by gender and race/ethnicity composition as for the PHS 398 Inclusion Enrollment Report form (http://grants.nih.gov/grants/funding/phs398/enrollmentreport.pdf). Group clinical trials by phase of study.
Template Table 8. Operational Timelines for Activation of Clinical Trial Proposals: List timelines for the LAO and any AOs (if applicable).
Template Table 9. Patient Accrual for Individual Clinical Trials: List actual timelines for specific steps in the clinical trial protocol development process, including accrual rate projected and achieved, total accrual, and study duration.
Template Table 10. Summary of Biomarker and Correlative Studies: List biomarker assays and other correlative laboratory studies performed on patient tissue during the previous 5 years, especially those that included surgical or image-guided biopsies.
Template Table 11. List of Procedures and Policies: List the relevant Standard Operating Procedures (SOPs) and LAO policies including, but not limited to: specimen acquisition and handling; tumor banking procedures and policy; Institutional Review Board (IRB) policies, Human Subjects Research Protections (HSRP) policies, safety, and pharmacovigilance procedures and policies, assay validation procedures, etc.
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:
Research Strategy: The Research Strategy should consist of the following sub-sections.
A: Overview of Relevant Capabilities and Past Performance
In this sub-section, applicants should summarize their ability and experience to conduct clinical trials and experimental therapeutic agent development. Describe relevant clinical and research activities related to the development of investigational agents either held under IND in collaboration with the NCI or performed as part of other academic pursuits.
B: Scientific Leadership and Site Organization
In this Sub-section, describe the qualifications and experience of the scientific leadership, their plans for participating in ET-CTN activities, and the organization of the proposed ET-CTN site.
Specifically, applicants are required to address, at a minimum, the following aspects:
Scientific Leadership
ET-CTN Site Organization:
C: Team Science for Project Development
ET-CTN sites will be expected to lead and/or participate in multi-disciplinary scientific teams during the development and implementation of ET-CTN drug development plans. In this section, describe relevant experience of the applicant team in the conduct and management of team science projects. Address plans with regard to such aspects as:
Provide an example of an inter- and trans-disciplinary team project focused on early drug development (ongoing or previously completed). The example should demonstrate cooperation and coordination among investigators across disciplines in the investigation of a research question in a coherent fashion. The roles for each team member and the methods and/or processes that the team utilizes to promote a team effort in answering complex research challenges should be clearly articulated. These activities should demonstrate enhancements of existing capabilities and new approaches to reach the goals of the collaborative team.
This example may include, but is not limited to, the description of activities such as:
The example to be provided is for purposes of peer review only. There is no expectation that the project described will be implemented or funded within the ET-CTN. It will serve as a representative example of the groups ability to select and constitute a highly multi-disciplinary team project. Examples that go beyond the LAO to include organizations involved in early phase experimental therapeutics are encouraged.
D: PK/PD, Biomarker Assays, and Molecular Characterization of Patients
In this section, outline expertise in PK/PD and acquisition/analysis of clinical specimens. Describe unique molecular characterization capabilities available at ET-CTN sites that can be utilized to analyze patients on ET-CTN trials. Address such elements as:
For patient molecular characterization, applicants should describe their expertise in the acquisition and analysis of high quality clinical specimens. Describe also experience, expertise, and procedures for validating and conducting studies using genomics, expression, analysis, or other assay-driven integral biomarker evaluations such as:
E: Coordination of Clinical Trials and Associated Activities
Applicants should describe their experience and the proposed management of complex early phase clinical trials, including protocol development, patient accrual, data and specimen management, and compliance with regulatory statutes. Clinical trials must be conducted in accordance with the Investigator's Handbook, A Manual for Participants in Clinical Trials of Investigational Agents Sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute (http://ctep.cancer.gov/handbook).
The application should address the items specified below:
Protocol Development and Clinical Trial Execution
Data Management
Regulatory Compliance
Data Formats
Protocol templates utilized by the ET-CTN should be referenced using appropriate websites such as the CTEP website, or included in the appendix.
F: Research Pharmacy Management
Describe plans for investigational pharmacy operations to fulfill obligations related to investigational agents. Summarize the existing/implemented and planned policies and procedures regarding the following elements:
Inter-institutional pharmacy exchange and secondary distribution of investigational drugs are NOT permitted.
G: Career Development and Mentored Training of Junior Investigators
A description of career development and mentored training in experimental therapeutics education and training for junior investigators (less than 7 years post oncology fellowship training) is required in this section. The proposed activities should include adequate mentorship and/or training for new and junior investigators that provides opportunities for the trainees to lead clinical trials and participate in future ET-CTN activities and/or initiatives. Training should provide opportunities to enhance skills in conducting clinical trials, skills in molecular pharmacology, and learn principles of clinical development of experimental therapeutics. Translational research ( bench to bedside and bedside to bench ) should be an integral part of these activities. Define and career development and mentored training activities in experimental therapeutics program for Junior Investigators.
The development of junior faculty through mentorship is expected to include such activities as:
Describe any relevant activities and opportunities that will be available to junior investigators in the environment of the proposed ET-CTN site:
Protection of Human Subjects: In addition to standard items indicated in the PHS 398 Application Guide, include in this Section SOPs and policies of the proposed ET-CTN related to study monitoring, data monitoring, and conflict of interest issues.
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modifications:
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.
Foreign (non-U.S.) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS 398 Application Guide.
(Note that the only foreign institutions eligible to apply in response to this FOA are Canadian institutions.)
Part I. Overview Information contains information about Key Dates.
Information on the process of receipt and determining if
your application is considered on-time is described in detail in the PHS 398
Application Guide.
Applicants may track the status of the application in the eRA Commons, NIH's electronic system for grants
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost
principles, and other considerations described in the NIH
Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH
Grants Policy Statement.
Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by the NCI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.
The overarching goal of this FOA is to bring novel anticancer agents into early
therapeutic clinical trials for cancer patients. This goal requires investigators
with outstanding leadership, robust infrastructure, and a strong record of
conducting clinical trials. Particularly important for the clinical development
of current generations of experimental cancer therapeutics is the ability to
integrate clinical trials with translational approaches and additional clinical
studies, including the ability to obtain and analyze PK/PD and biomarker data
in all patients enrolled on all studies. Essential for ET-CTN will be the
awardees' ability to work as part of a network. In this context, the important
aspects are whether the applicants have assembled a team of investigators
capable of conducting state-of-the-art early phase therapeutics trials and PD-pilot
studies in patients with cancer, and whether they will be able to work as a
coherent research team to efficiently and expeditiously conduct early phase
clinical trials.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the proposed ET-CTN site to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the ET-CTN site proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a program that by its nature is not innovative may be essential to advance a field.
Does the proposed ET-CTN site address an important problem or a critical barrier to progress in the field? If the aims of the proposed ET-CTN site are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific for this FOA: Will the ET-CTN site, as proposed, be able to introduce appropriate novel anticancer agents into oncology clinical trials in a timely, safe, and efficient manner?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the proposed ET-CTN site? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Specific for this FOA:
Does the project have adequate biostatistical expertise to conduct and analyze complex clinical and molecular data? How complete and comprehensive is the expertise of the PD(s)/PI(s) and the entire team of investigators assembled by the applicant(s) in terms of their ability to conduct state-of-the-art early experimental therapeutics studies in patients with cancer? How well do the research experience and qualifications of the PD(s)/PI(s) correspond to the need for multi-disciplinary capabilities (e.g., in medical oncology, radiation oncology, imaging, surgery) and across a broad range of cancer types?
Will these investigators be able to work as a coherent research team to efficiently and expeditiously conduct early phase clinical trials?
Do the PD(s)/PI(s) demonstrate the ability to facilitate collaborations between ET-CTN investigators and other clinical/translational science investigators?
Do the PD(s)/PI(s) have sustained, high-level participation in the scientific leadership of early experimental therapeutics (e.g., serving as scientific committee or protocol/trial study chairs, contributing new trial ideas including participating in LOI development, co-authoring publications on clinical trials research)?
What is the ability of the PD(s)/PI(s) to contribute in a meaningful way to the development of clinical trials in rare cancers?
How capable are the PD(s)/PI(s) of providing meaningful contributions to translational research, PK/PD, biomarker assays, and molecular characterization integral to or integrated into the ET-CTN clinical trials?
Do the PD(s)/PI(s) have adequate and appropriate experience in administering clinical trial research, including organization and management of the infrastructure required for patient recruitment/accrual, data collection, data reporting, and safety monitoring for patients enrolled on clinical trials?
Are the other key personnel appropriately trained and well suited to carry out the work associated with early clinical trials?
Is there sufficient and appropriately experienced support personnel available for the proposed ET-CTN site with the skills needed to develop, implement, and analyze early phase experimental therapeutic clinical trials?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Specific for this FOA:
Do the applicants propose novel or improved ways and/or methods to enhance or better conduct early clinical trials?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented?
If the project is in the early stages of development, will the strategy
establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?
Specific for this FOA:
Are the overall strategy, methodology, and analyses well reasoned and appropriate to accomplish the specific aims of the ET-CTN site?
How strong are the overall approaches proposed for individual components of the ET-CTN?
Do the research plans demonstrate an appropriate understanding of research opportunities in drug development and of the methodologies available to exploit these opportunities?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Relevant Capabilities and Past Performance
How strong are the applicants expertise and experience in early phase clinical trials for patients with cancer? Specifically, how adequate is this experience in terms of collection, management, and analysis of data from single institution or multi-institution clinical trials? What is the level of applicants experience in performing independent response auditing?
How productive were the applicants in terms of the timeliness of the development, implementation, and completion of recently conducted early phase clinical trials?
How accomplished are the applicants in terms of their research contributions (documented by peer-reviewed publications) to multi-institutional early phase experimental therapeutic clinical trials and dissemination of the results of such research?
Leadership, Governance, and Site Organization
To what extent are the proposed leadership and governance structure, decision-making processes, and interactions among key investigators optimal for designing and conduct of multi-disciplinary, multi-institutional clinical trials in a range of cancer types and special populations?
For applications designating multiple PD/PIs, is the leadership approach, including the designated roles, responsibilities, governance, and organizational structure consistent with the aims of the project and the expertise of each of the PD/PIs?
How well are defined the plans for an appropriate governance structure to coordinate activities related to the ET-CTN across the various disciplines and departments at the LAO institution?
Are the proposed leadership efforts and activities reasonably distributed across such areas as patient enrollment, clinical data collection and management? Are these efforts optimally balancing the various disciplines and the roles of clinical departments involved in the clinical trials at the proposed ET-CTN site)? Are these plans in line with the proposed workload and anticipated accrual to clinical trials to ensure/enhance participation in ET-CTN trials by various disciplines at the LAO?
Is the staffing plan appropriate to ensure the efficient governance of the proposed ET-CTN site?
Are the organizational plans for the LAO sufficient and optimal to ensure the LAO's ability to develop, propose, implement, and monitor ET-CTN clinical trials?
How appropriate is the proposed organization to ensure monitoring the performance of the affiliated clinical sites (AOs) in an ongoing manner?
How adequate is the ET-CTN organization in terms of supporting other aspects of early clinical trials and related activities? How well is the organization of the proposed ET-CTN site matched to its leadership (especially for applications designating multiple PD/PIs)?
Team Science for Project Development
How strong is the potential of the applicants for team science approaches to developing and implementing ET-CTN's early phase experimental therapeutic studies?
At what level will the proposed ET-CTN site be able to participate (and/or lead) inter- and trans-disciplinary team-based research efforts, including potential for interactions with investigators from other ET-CTN sites, other NCI-sponsored programs, and NCI staff members?
PK/PD, Biomarker Assays, and Molecular Characterization of Patients
Are the proposed plans and capabilities for incorporating PK/PD, and pharmacogenomic endpoints into the clinical trials appropriate and sufficient?
Are the proposed plans and capabilities for incorporating molecular characterization endpoints into the clinical trials appropriate? In particular, is the scope of such efforts sufficient, given the goal to include in these characterizations a high fraction of patients participating in clinical trials? Are the plans and capabilities for incorporating imaging endpoints into the ET-CTN's overall research program sufficient? How strong is the applicants understanding of the potential of imaging studies to aid drug development?
Coordination of Clinical Trials and Associated Activities
Protocol Development and Clinical Trial Execution. How appropriate are the overall coordination efforts for ensuring timely development of clinical trial protocols and clinical trial execution? Are the measures planned to maintain the proficiency of institution personnel in the management of early phase experimental therapeutic clinical trials clearly defined and sufficient? How appropriate and adequate are the mechanisms of periodic review of QA/QC, data management procedures, and safety monitoring? Will the proposed ET-CTN site have appropriate statistical expertise and support? How appropriate are study designs for early phase experimental therapeutic clinical trials that the applicants used previously? How appropriate are statistical designs for early phase clinical trials proposed for the ET-CTN? Do the ET-CTN sites have sufficient statistical support and utilize appropriate statistical design approaches for early experimental therapeutic clinical trials?
Correlative Studies. Does the applicant demonstrate the ability to obtain, process, and store high-quality specimens? Does the applicant demonstrate the ability to analyze and report on specimens from PK/PD and/or molecular characterization studies?
Data Analysis, Quality Assurance/Quality Control, and Reporting. Are the applicants capabilities for the analyses of data from multi-institutional clinical trials sufficient for the expected scale of activities? Does the application demonstrate adequate procedures to monitor and analyze the data and assure the safety of patients/participants? Are the QA/QC procedures adequate and sufficient to ensure the accuracy, integrity, and security of clinical trials data? Does the application demonstrate adequate procedures to review, analyze, and report data on serious and expedited adverse events? Are procedures for reporting of data from early phase clinical trials to CTEP using CTMS electronic data capture system sufficiently timely and reliable? Are all the critical needs for the required regulatory compliance adequately addressed?
Research Pharmacy Management
Are the resources, facilities, and equipment for research pharmacy management (including appropriate secure storage units) sufficient and in line with all applicable regulations? Do the proposed plans adequately address the needs for proper procedures for handling of experimental agents and maintaining all associated documentation? How complete is evidence that Research Pharmacy in the proposed ET-CTN site will (a) adhere to all applicable regulations with regard to investigational agent handling, (including transport and disposal); and (b) will maintain proper documentation and record keeping, transport, etc?
Career Development and Mentored Training of Junior Investigators
Is there adequate institutional commitment to mentorship, training, and support of junior investigators in experimental therapeutics? What are the overall quality and expected effectiveness of the mentoring plans? How well do the plans incorporate the opportunities for junior investigators to learn the principles of early clinical development of experimental therapeutics and participate (or lead) relevant clinical trials, participate in scientific committees, etc? How sufficient is the intended training in translational research? How valuable are for the ET-CTN goals other training and educational opportunities available to junior investigators?
Protections for Human Subjects
For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed ET-CTN site involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Not Applicable
Not Applicable
Not Applicable
As applicable for the ET-CTN site proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
How well are the applicants' budget projections aligned with the program objectives and proposed scale of operation? Are the funding allocations for PK/PD studies reasonable, appropriate, and not duplicative of other institutional funding?
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted response to this FOA.
Applications will be assigned to the NCI and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee's business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to the DUNS, SAM
Registration, and Transparency Act requirements as noted on the Award
Conditions and Information for NIH Grants website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
The following special terms of award are in addition to, and
not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant
administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable
when State and local Governments are eligible to apply), and other HHS, PHS,
and NIH grant administration policies.
The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
An NCI Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members may be designated to have substantial involvement (e.g., in the role of Project Managers). The NCI Project Scientist(s)/Managers(s) will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.
Additionally, an NCI program director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Some Program Officials may also have substantial programmatic involvement (as Project Scientists/Coordinators). In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek NCI waiver as stated above.
The main responsibilities of substantially involved NCI staff members include, but are not limited to, the following activities:
The NCI will have access to all data (including imaging data) collected and/or generated under this Cooperative Agreement and may periodically review the data. The NCI may also review all records related to awardees performance under the award for appropriate collection, review, and distribution of biospecimens collected in association with ET-CTN trials.
In case of insufficient patient accrual per the protocol specified, inability to meet the scientific aims of the Cooperative Agreement, or noncompliance with the Terms and Conditions of Award, the NCI reserves the right to reduce award budget, withhold support, suspend, or terminate the award.
Areas of Joint Responsibility
The cooperative agreement awardee shall, with CTEP assistance, develop appropriate early phase experimental therapeutic clinical trial protocols. Principal Investigators (PIs) of the ET-CTN awards, NCI ET-CTN Director(s), and CTEP Senior Investigators (Project Scientists) will be members of the ET-CTN.
ET-CTN sites will be expected to participate as active team members on drug development project teams. They will meet quarterly to review studies performed under the award and more often to participate on and provide input for the IDSC, with respect to the development of drug development plans. Areas of joint responsibility include:
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the ET-CTN Group representatives chosen from the ET-CTN Leadership without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
Note that in addition to these general rules for dispute resolution, a specific appeal process will be in place for decisions regarding approval of ET-CTN study proposals and the types of studies supported by the ET-CTN.
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone (301) 710-0267
Email: firstname.lastname@example.com
eRA Commons Help Desk (Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: (301) 402-7469 or (866) 504-9552 (Toll Free)
Email: firstname.lastname@example.com
S. Percy Ivy, M.D.
Investigational Drug Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
NCI Shady Grove
Room 5W458, MSC 9725
9609 Medical Center Drive
Bethesda, MD 20892-9725 (for Express mail, use Rockville, MD 20850)
Telephone: (240) 276-6107
Email: email@example.com
Referral Officer
Division of Extramural Activities
National Cancer Institute
9609 Medical Center Drive, Room 7W412
Bethesda, Maryland 20892-9750 (for Express mail, use Rockville, MD 20850)
Telephone: 240-276-6390
Fax: 240-276-7682
E-mail: email@example.com
Shane Woodward
Office of Grants Administration
National Cancer Institute
9609 Medical Center Drive
West Tower, 2W462
Rockville, MD 20850
Telephone: 240-276-6303
e-mail: firstname.lastname@example.com
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
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text:
The IndyCar Series won't return to Las Vegas Motor Speedway next season, and its future at the track depends in part on what it learns from the investigation into Dan Wheldon's fatal accident.
Wheldon, a two-time Indianapolis 500 winner, was killed in the opening laps of the Oct. 16 season finale at Las Vegas. The investigation into the 15-car fatal accident is ongoing, and IndyCar has postponed releasing its 2012 schedule until it determines if the series can continue racing on high-banked ovals such as Las Vegas.
Speedway Motorsports Inc. owner Bruton Smith was adamant he wanted IndyCar to honor the three-year lease deal it has with Las Vegas, but IndyCar CEO Randy Bernard had been reluctant to return to the speedway.
Smith told The Associated Press on Thursday that SMI agreed to a buyout of 2012, and the final season of the contract will be reviewed later.
Bernard confirmed he'd come to an agreement with SMI.
"We're not guaranteeing we'll be back," Bernard said. "But we'll test there, and we'll see what we can learn."
No matter the results, concerns remain about the emotional issues the series would face upon returning to Las Vegas.
Wheldon was killed 12 laps into the season finale in a fiery 15-car accident. Critics have pointed to everything from the 34-car field, the size and speed of the track, the speedway's high banking and the varying experience level of the drivers as reasons for the accident.
Wheldon was entered as part of a promotion that would have paid him $5 million if he could have driven from the back of the field to Victory Lane. It was all part of a season-ending spectacular aimed to boost television ratings and send IndyCar into 2012 with some momentum. Instead, it turned terribly wrong minutes into the race, and IndyCar has been struggling with difficult decisions and a tumultuous offseason in the seven weeks since.
"The IndyCar Series is in the midst of extensive research into the suitability of Indy Cars racing at our speedway," track president Chris Powell said.
"We believe it's in everyone's best interest to give the experts at IndyCar as much time as possible to compile their findings and conduct tests with the new car here at the speedway before we host another IndyCar event. We are very hopeful that the Indy Cars will return to Las Vegas Motor Speedway in 2013."
With Las Vegas settled, for now, attention now turns to Texas Motor Speedway.
The high-banked oval is one of the most popular venues in the series and has hosted IndyCar every year since 1997. But there was no sanctioning agreement in place before Wheldon's accident, and Bernard has been hesitant to complete a deal until the investigation is complete.
The uncertainty has TMS president Eddie Gossage frustrated, but he said Thursday recent conversations with Bernard had been productive.
"We don't have a deal yet, but that's not to say we aren't going to get one done," Gossage said. "Certainly we'd like to get this wrapped up, and I believe we'll be able to find a way to do just that."
Smith has been more outspoken, questioning why IndyCar is now concerned about one of its strongest venues. Although he was pleased to have Las Vegas resolved, Smith urged Bernard to make a decision on Texas soon.
"We're good to go on Las Vegas, and we'll still race the road course at (SMI-owned) Infineon, but I don't know what he's done with Eddie," Smith said. "Eddie is getting very frustrated and wants this resolved."
Texas last year hosted a highly-trumpeted twinbill by splitting its 500-mile race into a pair of 250-milers. Gossage has indicated he'd like another twinbill, perhaps with tweaks over length of the races or points awarded.
Not including Texas, the schedule currently has 14 events that have been previously announced by the tracks or the series. There's some concern over the Labor Day weekend event at Baltimore because the current promoters are saddled in debt and likely will have to give up control of the event in order for it to continue
IndyCar has not indicated when it will announce its 2012 schedule or if it will replace Las Vegas. Should Bernard not find something to slot in as a new season finale, the season would end in early September at Auto Club Speedway in Fontana, Calif.

subset: commoncrawl


text:
Finally Trying Lahey No-Knead Technique
I've been hemming and hawing for a while about trying the Lahey technique, but when I managed to find an interesting ceramic cooking vessel for $7 at a thrift store ....
.... I thought it was time to give it a go.
Used an 80% hydration dough, with a pain de campagne combination of flours (88% unbleached white, 6% whole wheat, 6% dark whole wheat rye) in a 475 degree oven, 30 minutes covered and 30 minutes uncovered.
The top-of-post shot shows the crust I got - very happy with that.
Here's what the crumb ended up looking like:
Very nice crust, but I was hoping for a bit more more of an open crumb. Still a damned tasty loaf (to be the starch side for a fresh tomato salad), but any advice re: getting a more open crumb would be appreciated.


text:
Kitchen Gallery: Bright White + Warm Wood
We are preparing to move to a new apartment, and although we have been known for having a colorful kitchen, our plans for the new space are quite different. Perhaps it's symbolic of the fresh start, or maybe we're inspired by the sunny windows in our new kitchen, but we keep imagining bright white walls with warm wood countertops, shelves, or other details. Here are some of the lovely examples we've bookmarked for inspiration. What do you think? Do you have – or dream about – a kitchen with these elements?
• 1 White with wood at Living Etc
• 2 Custom kitchen at Country Living
• 3 Seaside kitchen at Country Homes & Interiors
• 4 White Walls and Pine Cupboards at Country Living
• 5 White shelving at Living Etc
• 6 Relaxed kitchen at Living Etc
• 7 Wood countertops at Country Living
• 8 Garden View at Sunset
• 9 Small white kitchen/diner at Ideal Home
• 10 Rustic white kitchen at Living Etc
Related: Kitchen Gallery: White, Bright, and Clean
(Images: Living Etc, James Merrell/Country Living, Country Homes & Interiors, Wendell Weber/Country Living, Living Etc, Living Etc, Grey Crawford/Country Living, John Clark/Sunset, Ideal Home, Living Etc)


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April 26, 2013
NVivo site license for K-State personnel and graduate students
Working on ethnographic field data? Just finished conducting a large-scale online survey? Exploring grounded theory? Engaged in action research? Portraiture?
Analyzing data and information from a range of digital data types? Conducting a qualitative meta-analysis?
Working on a qualitative or mixed methods thesis, dissertation, or manuscript?
K-Staters conducting qualitative and mixed methods research and engaging in data analytics now have another software tool to enhance their work.
NVivo enables researchers to collate, organize and manage a range of digital data: Audio files, videos, photos, texts, and data sets. Users are able to code data and identify themes in their work using various analytical tools. They may memo and annotate digital contents. They may search for and retrieve data; they may link data.
Further, they may use NVivo to create data visualizations — spatial diagrams and graphs — and mind maps. A new feature of NVivo 10, called NCapture, enables some limited data extractions from dedicated social media platforms. Finally, users may also use this tool for theory development.
A K-State campus site license for NVivo 10
K-State recently purchased a campus site license for NVivo 10, a qualitative and mixed methods data analytics software, for its faculty, staff, administrators, and graduate students, who may download the software from the protected site after signing in with their eID/password. To activate the software, users will need the unique K-State license key. The software is only for that individual's professional use and may be installed on up to two computing devices, typically a desktop machine and a laptop.
Computing system requirements
The current version of this software runs on PCs with the following recommended system requirements. This may also be installed on Macs running virtual machines or parallels.
NVivo 10 forthcoming for Mac computers
A Mac version is due out in late 2013; this software version is going through testing currently. At the time of the Mac version release, all those on this K-State site license may download the Mac version as well. More details about that download will be forthcoming closer to the official release date.
Getting started with NVivo 10
Web-based trainings are part of this site license package.
- Live NVivo e-demonstrations dates
- Recorded NVivo demonstration
- Free Resources to learn how to use NVivo
- NVivo training options
Additional trainings are offered by QSR International.
For help with the installation, contact the IT Help Desk at 785-532-7722 or email@example.com.


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Out of respect to Jerry send your telethon dollars to [email protected]
TUCSON, Ariz. — Comedian Jerry Lewis is no longer serving as the Muscular Dystrophy Association's national chairman and won't be appearing on this year's Labor Day telethon, the nonprofit agency announced Wednesday night.
Lewis, 85, has been the MDA's national chairman since the early 1950s and has hosted the Labor Day Muscular Dystrophy Association telethon since 1966.
He announced in May that he was retiring as host of the telethon that has become synonymous with his name. But Lewis added that he planned to make his final appearance on this year's Sept. 4, show and planned on continuing to serve as MDA's national chairman.
MDA Chairman of the Board R. Rodney Howell said in a statement that Lewis "will not be appearing on the telethon" and "we will not be replacing him as MDA national chairman."
Howell added that Lewis "is a world-class humanitarian and we're forever grateful to him for his more than half century of generous service to MDA."
The statement did not provide any further explanation for the moves, and calls to the Tucson, Ariz,-based nonprofit weren't immediately returned Wednesday night. Representatives for Lewis, a publicist and a manager, also did not immediately respond to messages left for comment.
Lewis, a Las Vegas resident, has in recent years battled a debilitating back condition, heart issues and the crippling lung disease pulmonary fibrosis.
MDA officials said more than $1 billion has been raised during Muscular Dystrophy Association telethons over the years and a national network of some 200 hospital-affiliated clinics has opened since Lewis became involved in the telethon.
Lewis' first live Labor Day weekend telethon in 1966 was broadcast by a single New York City television station. It raised more than $1 million in pledges.
The telethon moved from New York to Las Vegas in 1973 and had stints in Los Angeles before returning in 2006 to Las Vegas.
Last year's Jerry Lewis MDA Telethon aired from the South Coast hotel-casino on the Las Vegas Strip and was broadcast by more than 170 stations. It raised almost $59 million to fund research to find a cure for muscular dystrophy and ALS, or Lou Gehrig's disease.
The live telethon usually lasts 21 1/2 hours. Sometimes Lewis would sing or tell lighthearted jokes. He introduced guests and other performers like a ringmaster. Sometimes, he turned serious and shared stories of people afflicted by the disease or who were helped by the association. All the while, he urged donors to contribute while a tote board rang up pledge totals.
Some telethon moments have made history.
In Las Vegas during the 1976 telethon, Lewis was reunited by Frank Sinatra with Dean Martin, with whom the comedian had an acrimonious split 20 years earlier. The famous entertainer best known for his slapstick humor first teamed with Martin in the 1940s to play nightclubs and television shows and to make a series of comedy films.


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Norovirus (Norwalk Virus)
Noroviruses are the most common cause of acute gastroenteritis (infection of the stomach and intestines) in the United States. Norovirus illness spreads easily and is often called stomach flu or viral gastroenteritis,People who are infected can spread it directly to other people, or can contaminate food or drinks they prepare for other people. The virus can also survive on surfaces that have been contaminated with the virus or be spread through contact with an infected person.
Sources | Produce, shellfish, ready-to-eat foods touched by infected food workers (salads, sandwiches, ice, cookies, fruit), or any other foods contaminated with vomit or feces from an infected person |
Incubation Period | 12-48 hours |
Symptoms | Diarrhea, vomiting, nausea,and stomach pain. Diarrhea tends to be watery and non-bloody. Diarrhea is more common in adults and vomiting is more common in children |
Duration of Illness | 1-3 days. Among young children, old adults, and hospitalized patients, it can last 4-6 days. |
What Do I Do? | Drink plenty of fluids and get rest. If you cannot drink enough fluids to prevent dehydration, call your doctor. |
How Do I Prevent It? |
General Information
Norovirus Infection (National Institute of Allergy and Infections Diseases)General information on causes, symptoms, treatment, and prevention.
Norovirus (CDC)
General information, including questions and answers, as well as information for food handlers and healthcare facilities.
Norwalk virus family (FDA)
From the Bad Bug Book; provides basic facts, including associated foods, frequency of disease, complications, and target populations.
Facts About Noroviruses on Cruise Ships (CDC)
Find out why norovirus outbreaks are associated with cruise ships.
Norovirus: Facts for Food Handlers (CDC)
How norovirus is spread through foods and tips for preventing its spread.
How norovirus is spread through foods and tips for preventing its spread.


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Compiled by Devin D. O'Leary. Email your weird news to email@example.com.
Latest Article|September 3, 2020|Free
::Making Grown Men Cry Since 1992
5 min read
Dateline: EnglandA groom has been sentenced to one year in prison after calling in a fake bomb threat on his wedding day—because he forgot to book the venue. Neil McArdle, 36, was in charge of securing St. George's Hall in Liverpool for his wedding on April 26. The night before the ceremony, however, McArdle realized he had forgotten to mail in the form. Shortly after his bride, Amy Williams, woke up on the day of the ceremony, McArdle slipped out of the house and called the Liverpool Register Office. Using a disguised voice, he told the secretary, "This is not a hoax call. There is a bomb in St. George's Hall and it will go off in 45 minutes." The call, which came 11 days after the Boston Marathon bombing, provoked a full-scale civil emergency, leaving McArdle and Williams stranded outside the venue. Unfortunately the building was cleared in less than an hour, allowing all ceremonies to continue as scheduled—except the McArdle-Williams nuptials, which were not officially booked. McArdle was arrested later that day when police traced the call to his personal cell phone. Earlier this month, a judge at Liverpool Crown Court told McArdle the bride "was getting ready, expecting you were going to be man and wife and a very solemn public event in her life and you knew that was not going to take place. You did not say, 'We need to talk.' You tried to weasel your way out by creating a bomb hoax so the wedding wouldn't take place." To the man's credit, McArdle's fiancee has stood by him, even after his sentencing.Dateline: EnglandA pub in the English village of Stilton has been told it's illegal to market its cheese as "stilton" cheese. Though the blue-veined cheese made at The Bell Inn is technically stilton and comes from Stilton, European Union, regulations restrict use of the word. According to EU rules, the name stilton can only be applied to cheese made in the English counties of Leicestershire, Derbyshire and Nottinghamshire. Stilton lies outside that area. Though Stilton gave its name to the sharp-tasting English cheese, historians are divided on whether the foodstuff was traditionally made there. Local cheese makers have asked the government to amend the Protected Designation of Origin rules to include Stilton. "It's ridiculous that we can't make stilton in Stilton," said Bell Inn landlord Liam McGivern. For the time being, McGivern's cheese is being sold as "Bells Blue."Dateline: FloridaThe Tampa Bay Times reports a woman was shot in the leg by the same bullet a man used to kill himself. Authorities say Jeane Sams was visiting her cousin's condo complex in Port Richey on Wednesday, Oct. 17. The family was inside the apartment watching Monsters, Inc. and eating pizza rolls when Sams got a call on her cell phone. She stepped outside to take it, and the family heard a sound "like a firecracker." Sams came back into the condo, blood gushing from her right knee. "I got shot," she told her family. According to the Pasco County Sheriff's Office, the bullet had just come from Michael Bruty's head. Bruty, 28, was arguing with his girlfriend several yards up the road. The argument ended with Bruty putting a gun to his head and pulling the trigger. Police received two 911 calls that evening and were quickly able to connect the two incidents once the gun was recovered from underneath Bruty's body. Bruty died at the scene. Sams was taken to Regional Medical Center Bayonet Point and was released later that week.Dateline: TennesseeA small-town police officer has lost his job after shooting up a dollar store in an attempt to kill a squirrel. According to police documents, Officer Jody Putnam was inside the Dollar General Store in Mountain City when employees noticed a squirrel loose in the building. Putnam allegedly fired at least one shot at the animal with his handgun. When that didn't work, he pulled out a can of pepper spray and went to work. "There were a lot of people that come out and just like me they came out and they were coughing and a-hacking," property owner Carl Duffield told WJHL-TV. "It was comical, but I'm sure they didn't feel that way." Officers in Mountain City are required to file a report whenever they discharge a weapon. Putnam refused to do so and was fired for the violation by the town's Board of Mayor and Alderman.


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Education is economic development. Encouraging young scholars to flourish, thereby
benefiting the global society, embodies the true spirit of this incredible institution.
The Economic Impact Report highlights just a few of ULM's significant contributions to greater Louisiana, the surrounding region, and the country. You will discover the breadth of our reach in the professional services provided by our faculty, staff and students, the innovative research conducted by our faculty, and the volunteer hours regularly contributed by our university family.
Much of what we contribute to the state and region is unique to our institution. For example, our nationally renowned School of Education's Louisiana Leader Fellows Program, hailed by the Governor as the premier program in the state, empowers talented teachers to become principals in their schools.
In addition, ULM's School of Pharmacy, Louisiana's only state-supported program, continues to produce the best professionals in the field, and our nursing students continue to score significantly higher than the national average on exit exams.
These programs and many others exemplify an impressive and growing tradition of excellence. We are also constantly evolving and expanding our idea of the university. For example, we are strengthening our state by providing courses to the 600,000 Louisiana adult learners who have earned college credits but have not completed their degrees.
ULM's online degree program — eULM — strives to educate today's "anytime, anywhere" student. Our new online health studies degree prepares professionals for mid-level management positions in a variety of health care organizations and increases the capabilities of our state's workforce. That kind of educational outreach is the cornerstone of economic development. By making higher education available to all Louisianians, we are ensuring a brighter economic future and quality of life for our entire state and region.
Another part of our story, our commitment to northeastern Louisiana, is exemplified in the revitalization of our university — both within and beyond our classrooms. By 2010, we will have spent more than $80 million in classroom upgrades and campus improvement projects in an effort which was launched in 2002. That is a direct and concerted investment in our students and in northeastern Louisiana. In addition, our professors continue to expand their methodologies, and many now incorporate emerging technologies into their curriculums.
Finally, ULM contributes to something quite incredible: the vitality of our state and region. Investing in higher education is crucial to our economic future because it means we envision a potential for growth and new possibilities for Louisiana.


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B::Disassembler - Disassemble Perl bytecode
use Disassembler qw(print_insn); my $fh = new FileHandle "<$ARGV[0]"; disassemble_fh($fh, \&print_insn);
disassemble_fh takes an filehandle with bytecode and a printer function. The printer function gets three arguments: insn, arg (optional) and the comment.
See lib/B/Disassembler.pm and scripts/disassemble.
disassemble_fh takes an filehandle with bytecode and a printer coderef.
Two default printer functions are provided:
print_insn print_insn_bare
Callback function for disassemble_fh, which gets three arguments from the disassembler. insn (a string), arg (a string or number or undef) and the comment (an optional string).
This supports the new behaviour in scripts/disassemble. It prints each insn and optional argument with some additional comments, which looks similar to B::Assembler with option -S (commented source).
This is the same as the old behaviour of scripts/disassemble. It prints each insn and optional argument without any comments. Line per line.
Returns the .plc header as array of
( magic, archname, blversion, ivsize, ptrsize, byteorder, longsize, archflag, perlversion )
in ARRAY context, or in SCALAR context the array from above as named hash.
magic is always "PLBC". "PLJC" is reserved for JIT'ted code also loaded via ByteLoader.
archname is the archname string and is in the ByteLoader up to 0.06 checked strictly. Starting with ByteLoader 0.06_05 platform compatibility is implemented by checking the $archflag, and doing byteorder swapping for same length longsize, and adjusting the ivsize and ptrsize.
blversion is the ByteLoader version from the header as string. Up to ByteLoader 0.06 this version must have matched exactly, since 0.07 earlier ByteLoader versions are also accepted in the ByteLoader.
ivsize matches $Config{ivsize} of the assembling perl. A number, 4 or 8 only supported.
ptrsize matches $Config{ptrsize} of the assembling perl. A number, 4 or 8 only supported.
longsize is $Config{longsize} of the assembling perl. A number, 4 or 8. Only since blversion 0.06_03.
byteorder is a string of "0x12345678" on big-endian or "0x78563412" (?) on little-endian machines. The beginning "0x" is stripped for compatibility with intermediate ByteLoader versions, i.e. 5.6.1 to 5.8.0, Added with blversion 0.06_03, and also with blversion 0.04. See BcVersions
archflag is a bitmask of opcode platform-dependencies. Currently used: bit 1 for USE_ITHREADS bit 2 for MULTIPLICITY Added with blversion 0.06_05.
perlversion $] of the perl which produced this bytecode as string. Added with blversion 0.06_06.
Malcolm Beattie MICB at cpan.org (retired), Reini Urban email@example.com since 2008.
MICB at cpan.org
To install B::C, copy and paste the appropriate command in to your terminal.
cpanm B::C
CPAN shell
perl -MCPAN -e shell install B::C
For more information on module installation, please visit the detailed CPAN module installation guide.


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Printed circuit board ties are made from the same copper clad material used in fabricating electronic circuits. PC ties simplify crossing and turnout contruction since stock rails, guard rails and frogs can be soldered in place to hold gauge. PC ties are cut to length by the modeler using a razor saw, rail nippers, diagonal cutters or a cutting disc on a motor tool. PC ties can be used to replace every fifth wood tie in track work and thus eliminate hand spiking. Once everything is soldered in place, the copper can be cut between the rails, insuring that the rails are insulated from each other. The substrate, or base material, holds everything in place after the copper coating is cut. PC tie material comes in 12" lengths to minimize waste as the ties are cut to match the various lengths needed. Our PC ties strips are copper clad on both sides.
One package of ten 12" long PC tie strips sheared to a scale 8" width (.167" actual) from .068 board. For use with scale 6" x 8" wood ties, O scale PC Ties will need spacers to match the height of regular wood ties.